Printed on: Sat Jun 26 2021, 05:47:13 AM Official Status: Currently Official on 26-Jun-2021 DocId: 1_GUID-BF41B99E-B619-405D-8604-C8B6BB9E0E1D_5_en-US

(EST)
Printed by: Nguyen Nhan Official Date: Official as of 01-May-2021 Document Type: USP @2021 USPC
1

rU = peak response of acebutolol from the Sample

Acebutolol Hydrochloride solution
rS = peak response of acebutolol from the Standard
solution
CS = concentration of USP Acebutolol
Hydrochloride RS in the Standard solution
(mg/mL)
CU = concentration of Acebutolol Hydrochloride in the
Sample solution (mg/mL)

C18H28N2O4 · HCl 372.89 Acceptance criteria: 98.0%–102.0% on the dried basis

Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl) IMPURITIES
amino]propoxy]phenyl]-, monohydrochloride, (±)-; • RESIDUE ON IGNITION á281ñ: NMT 0.1%
(±)-3′-Acetyl-4′-[2-hydroxy-3-(isopropylamino)propoxy]-
butyranilide monohydrochloride [34381-68-5]. Change to read:
DEFINITION • ORGANIC IMPURITIES
Acebutolol Hydrochloride contains NLT 98.0% and NMT Solution A: Mix 2.0 mL of phosphoric acid and 3.0 mL of
102.0% of acebutolol hydrochloride (C18H28N2O4 · HCl), triethylamine, and dilute with water to 1 L.
calculated on the dried basis. Solution B: Acetonitrile and Solution A (50:50)
IDENTIFICATION Mobile phase: See Table 1.
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared

al
Spectroscopy: 197K Table 1
• B. The retention time of the major peak of the Sample Time Solution A Solution B
solution corresponds to that of the Standard solution, as (min) (%) (%)
obtained in the Assay. 0 98 2

Change to read:
• C. IDENTIFICATION TESTS—GENERAL á191ñ, Chemical
Identification Tests, Chloride: Meets the requirements of
ci 2

30.5

41
98

10

10
2

90

90
▲
the test for amine hydrochlorides▲ (USP 1-May-2021)
ffi
Standard stock solution 1: 0.2 mg/mL of USP Acebutolol
ASSAY Related Compound A RS prepared as follows. Dissolve a
Change to read: suitable amount of USP Acebutolol Related Compound A RS
in a suitable volumetric flask, in 50% of the total volume of
• PROCEDURE acetonitrile, and dilute with Solution A to volume.
Mobile phase: Methanol, glacial acetic acid, and a 0.3% Standard stock solution 2: 0.2 mg/mL of USP Acebutolol
O

aqueous solution of sodium dodecyl sulfate (675:20:325) Related Compound B RS prepared as follows. Dissolve a
▲
▲ (USP 1-May-2021) suitable amount of USP Acebutolol Related Compound B RS
Standard solution: 0.14 mg/mL of USP Acebutolol in a suitable volumetric flask, in 50% of the total volume of
Hydrochloride RS in water acetonitrile, and dilute with Solution A to volume.
Sample solution: 0.14 mg/mL of Acebutolol Hydrochloride Standard solution A: 0.002 mg/mL of USP Acebutolol
in water Hydrochloride RS in Solution A
Chromatographic system Standard solution B: 0.004 mg/mL of USP Acebutolol
(See Chromatography á621ñ, System Suitability.) Related Compound I RS in Solution A
Mode: LC Standard solution C: 0.002 mg/mL of USP Acebutolol
Detector: UV 254 nm Related Compound A RS in Solution A from Standard stock
Column: 3.9-mm × 30-cm; ▲10-µm▲ (USP 1-May-2021) packing solution 1
L1 Standard solution D: 0.004 mg/mL of USP Acebutolol
Flow rate: 2 mL/min Related Compound B RS in Solution A from Standard stock
Injection volume: 10 µL solution 2
System suitability System suitability solution: 0.4 µg/mL each of USP
Sample: Standard solution Acebutolol Hydrochloride RS and USP Acebutolol Related
Suitability requirements Compound I RS in Solution A from Standard solution A and
▲
▲ (USP 1-May-2021) Standard solution B
Tailing factor: NMT 2.5 Sample solution: 2 mg/mL of Acebutolol Hydrochloride in
Relative standard deviation: ▲NMT▲ (USP 1-May-2021) Solution A
0.73% Chromatographic system
Analysis (See Chromatography á621ñ, System Suitability.)
Samples: Standard solution and Sample solution Mode: LC
Calculate the percentage of acebutolol hydrochloride Detector: UV 240 nm
(C18H28N2O4 · HCl) in the portion of Acebutolol Column: 4.0-mm × 12.5-cm; 5-µm packing L1
Hydrochloride taken: Column temperature: 40°
Flow rate: 1.2 mL/min
Result = (rU/rS) × (CS/CU) × 100 Injection volume: 25 µL
System suitability
Samples: Standard solution A and System suitability solution

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Printed on: Sat Jun 26 2021, 05:47:13 AM Official Status: Currently Official on 26-Jun-2021 DocId: 1_GUID-BF41B99E-B619-405D-8604-C8B6BB9E0E1D_5_en-US
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Printed by: Nguyen Nhan Official Date: Official as of 01-May-2021 Document Type: USP @2021 USPC
2

Suitability requirements Table 2

Resolution: NLT 7.0 between acebutolol and acebutolol Relative Acceptance
related compound I, System suitability solution Retention Criteria,
Relative standard deviation: NMT 2.0%, Standard Name Time NMT (%)
solution A Acebutolol related
Analysis compound B▲▲
Samples: Standard solution A, Standard solution B, Standard (USP 1-May-2021) 0.72 0.2
solution C, Standard solution D, and Sample solution Acebutolol related
Calculate the percentage of acebutolol related compound compound I▲▲
A, acebutolol related compound B, and acebutolol related (USP 1-May-2021) 0.91 0.2
compound I in the portion of Acebutolol Hydrochloride
Acebutolol 1.00 —
taken:
Acebutolol related
Result = (rU/rS) × (CS/CU) × 100 compound A▲▲
(USP 1-May-2021) 1.48 0.1
rU = peak response of acebutolol related compound A, Any unspecified impuri-
acebutolol related compound B, or acebutolol —
ty 0.10
related compound I from the Sample solution
rS = peak response of acebutolol related compound A, Total impurities a — 0.5
acebutolol related compound B, or acebutolol a Total impurities include specified and unspecified impurities.▲
related compound I from Standard solution B, ▲ (USP 1-May-2021)

Standard solution C, or Standard solution D

SPECIFIC TESTS
CS = concentration of USP Acebutolol Related

al
• PH á791ñ
Compound A RS, USP Acebutolol Related
Compound B RS, or USP Acebutolol Related Sample solution: 10 mg/mL of Acebutolol Hydrochloride
Compound I RS in Standard solution B, Standard in water
solution C, or Standard solution D (mg/mL) Acceptance criteria: 4.5–7.0
CU = concentration of Acebutolol Hydrochloride in the
ci • LOSS ON DRYING á731ñ
Sample solution (mg/mL) Analysis: Dry at 105° for 3 h.
Acceptance criteria: NMT 1.0%
Calculate the percentage of any unspecified impurity in the ADDITIONAL REQUIREMENTS
portion of Acebutolol Hydrochloride taken: • PACKAGING AND STORAGE: Preserve in tight containers, and
store at controlled room temperature.
ffi
Result = (rU/rS) × (CS/CU) × 100 • USP REFERENCE STANDARDS á11ñ
USP Acebutolol Hydrochloride RS
rU = peak response of any unspecified impurity from USP Acebutolol Related Compound A RS
the Sample solution N-(3-Acetyl-4-hydroxyphenyl)butyramide.
rS = peak response of acebutolol from Standard C12H15NO3 221.25
solution A USP Acebutolol Related Compound B RS
O

CS = concentration of USP Acebutolol N-{3-Acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]

Hydrochloride RS in Standard solution A phenyl}acetamide.
(mg/mL) C16H24N2O4 308.37
CU = concentration of Acebutolol Hydrochloride in the
Sample solution (mg/mL) USP Acebutolol Related Compound I RS
N-{3-Acetyl-4-[3-(ethylamino)-2-hydroxypropoxy]
Acceptance criteria: See Table 2. ▲The reporting phenyl}butyramide.
threshold is▲ (USP 1-May-2021) 0.05%. C17H26N2O4 322.40

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